The c-raf-1 protooncogene is altered in several human malignancies. Research on Raf-1 has focused on its activation during cell cycle entry following cellular stimulation with mitogens. In preliminary studies I have found that the c-Raf-1 kinase is hyperphosphorylated and activated in mouse fibroblasts arrested in mitosis, suggesting that Raf-1 may play a role in the G2/M transition of the cell cycle as well. The following series of experiments are proposed: (1) Mapping and mutagenesis of the sites of mitotic Raf hyperphosphorylation (2) Identification of upstream effectors of Raf-I phosphorylation and activation (3) Characterization of downstream targets of activated Raf-I in mitosis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA068743-03
Application #
2517671
Study Section
Special Emphasis Panel (ZRG2-BIOL-2 (02))
Project Start
1997-08-17
Project End
Budget Start
1997-08-17
Budget End
1998-08-16
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Cornell University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Laird, A D; Morrison, D K; Shalloway, D (1999) Characterization of Raf-1 activation in mitosis. J Biol Chem 274:4430-9
Laird, A D; Shalloway, D (1997) Oncoprotein signalling and mitosis. Cell Signal 9:249-55